Hyper IgM Syndrome, X-linked (XHIM) – CD40L Deficiency
- Inheritance: X-Linked recessive
- Gene: CD40L
- Protein: CD40L
- Tests: CD40L Gene Sequencing, CD40 Ligand Protein by Flow
Key Clinical and Laboratory Features
- Common clinical features: Recurrent bacterial sinopulmonary infections, Pneumocytis jiroveci pneumonia (particularly in patients under age 5), chronic diarrhea (cryptosporidium is common and may lead to sclerosing cholangitis, liver cirrhosis and neuroendocrine malignancies in the abdomen), neutropenia
- Other clinical features: Autoimmunity including cytopenias, hypoparathyroidism, nephritis, and rheumatoid arthritis. Anemia due to chronic parvovirus B19 infection.
- Physical exam: Tonsils and lymph nodes are typically present. Lymphadenopathy and hepatosplenomegaly are common.
- Common laboratory features: No expression/function of CD40 ligand. Normal T-cell counts and B-cell counts. IgM levels are typically elevated but may be normal while IgG and IgA levels are very low.
|GENE||CD40L Gene Sequencing||The gold standard for confirming a diagnosis of CD40 ligand (CD40L) deficiency in a patient with suggestive symptoms and abnormal CD40 ligand protein flow.|
|PROTEIN AND FUNCTION||CD40 Ligand Protein by Flow||This is both a protein test and a functional test that uses two different monoclonal antibodies to determine whether CD40 ligand protein is expressed on the surface of activated T cells. It also utilizes a CD40-Ig fusion protein to determine if the expressed CD40 ligand protein is able to functionally bind to CD40. Because this test evaluates both CD40L protein and its function, it is able to identify at least 99% of patients with XHIM.|